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A diastereoselective trans-alkylation of aza-enolates of orthogonally protected chiral bis-lactim ethers with electrophiles, such as alkyl halides, and subsequent deprotection via hydrolysis/hydrogenation leads to dipeptide ester derivatives.

Aza-conjugate addition of the lithium anion of N-trimethylsilyl-p-methoxybenzylamine to tert-butyl enoate acceptors, in the presence of a stoichiometric amount of enantiopure 1,2-dimethoxy-1,2-diphenylethane and excess trimethylsilyl chloride, affords tert-butyl-N-p-methoxybenzyl-β-amino esters with excellent levels of enantiocontrol. These N-p-methoxybenzyl-β-amino-esters may be deprotected under oxidative conditions via treatment with ceric ammonium nitrate, followed by acid hydrolysis of the resultant imine intermediates, to afford enantiopure β-amino-esters containing hydrogenolytically sensitive functionality.

A clean, mild and sustainable method for the functionalization of pyridines and their analogues is reported. A zinc-based Lewis acid is used to activate pyridine and its analogues towards nucleophilic aromatic substitution, conjugate addition, and cyclization reactions by binding to the nitrogen on the pyridine ring and activating the pyridine ring core towards further functionalization.

The title compounds are obtained by reaction of aryl-aldehydes containing ortho-substituted α,β-unsaturated carboxylic acid derivatives with hydroxylamine leading to reactive N-hydroxy-carbinolamine intermediates which undergo intramolecular aza-conjugate addition reactions.

The 1,6-conjugate addition of nucleophiles to dienyl diketones produces either cyclopentenone or 2H-pyran products with high selectivity through either Nazarov (4π) or 6π electrocyclization, respectively. The outcome of the reaction is dependent upon the nature of the nucleophile used. Nucleophiles that are anionic or easily deprotonated exclusively produce cyclopentenones via Nazarov cyclization, whereas the neutral nucleophile DABCO promotes 6π cyclization to afford 2H-pyrans. Experimental evidence is presented for both retro-4π and -6π electrocyclization in these systems, lending support to the bifurcated mechanistic hypothesis proposed for these cyclizations.

The stereocontrolled introduction of the C6 and C12 vicinal quarternary centers via a [2 + 2]-photocycloaddition is reported.

A high yielding rearrangement of epoxy-esters, under Lewis acid conditions, to give bicyclic ortho esters is reported.

Acid chlorides can be activated by using simple iodide sources, e.g., KI or LiI, to undergo nucleophilic attack by a variety of relatively weak nucleophiles.

DFT calculations of UO2 oxidation indicate stable compounds U4O8.889, U3O7, and U3O7.333, which are based on ordering of split quad-interstitial clusters.

Bromocycloalkenone (II) is used as a potent dienophile in inter- and intramolecular Diels—Alder cycloadditions.

Treatment of a range of trisubstituted β,γ-unsaturated esters with 2 equiv of (−)-monoisopinocampheylborane results in hydroboration of their alkene functionalities and reduction of their ester groups to afford chiral 1,3-diols containing two new vicinal β,γ-( anti )-stereocentres in 67–85% enantiomeric excess.

α,β-Unsaturated imides, formylated at the nitrogen atom, comprise a new and valuable family of dienophiles for servicing Diels–Alder reactions. These systems are assembled through extension of recently discovered isonitrile chemistry to the domain of α,β-unsaturated acids. Cycloadditions are facilitated by Et2AlCl, presumably via chelation between the two carbonyl groups of the N-formyl amide. Applications of the isonitrile/Diels–Alder logic to the IMDA reaction, as well as methodologies to modify the N-formyl amide of the resultant cycloaddition product, are described. It is expected that this easily executed chemistry will provide a significant enhancement for application of Diels–Alder reactions to many synthetic targets.

The title compounds (II) react with primary and secondary alcohols to yield the corresponding esters.

Over the last ten years there has been a huge increase in development and applications of organocatalysis in which the catalyst acts as a nucleophile. Amidines and guanidines are often only thought of as strong organic bases however, a number of small molecules containing basic functional groups have been shown to act as efficient nucleophilic catalysts. This tutorial review highlights the use of amidine, guanidine, and related isothiourea catalysts in organic synthesis, as well as the evidence for the nucleophilic nature of these catalysts. The most common application of these catalysts to date has been in acyl transfer reactions, although the application of these catalysts towards other reactions is an increasing area of interest. In this respect, amidine and guanidine derived catalysts have been shown to be effective in catalysing aldol reactions, Morita–Baylis–Hillman reactions, conjugate additions, carbonylations, methylations, silylations, and brominations.

Treatment of unsaturated amides of type (I), (IV), and (IX) with NMO/OsO4 leads to triols which spontaneously undergo cyclization to afford biologically important optically active hydroxy-γ-butyrolactones.

Enolates of N-substituted amino esters (I) and (III) undergo intramolecular cyclization reactions to afford (syn)-aza-anions that undergo 4-exo-trig cyclization onto their ester carbonyl group to afford cyclic β-lactams (II) and (IV) in high diastereoselectivity.

One-step syntheses of nitrofuranyl benzimidazoles that are active against multidrug-resistant bacteria

A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure α-arylglycines has been developed. Addition of a range of aryl-aldehydes to a solution of sodium cyanide and (S)-1-(4-methoxyphenyl)ethylamine affords highly crystalline (S,S)-α-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-α-aminonitriles in 6 M aqueous HCl at reflux resulted in cleavage of their chiral auxiliary fragments and concomitant hydrolysis of their nitrile groups to afford enantiopure (S)-α-arylglycines. The enantiopurities of these (S)-α-arylglycines were determined via derivatization of their corresponding methyl esters with 2-formylphenylboronic acid and (S)-BINOL, followed by 1H NMR spectroscopic analysis of the resultant mixtures of diastereomeric iminoboronate esters.

The cyclopropane ring opening reaction is mediated by Hg(O-CO-CF3)2, leads after demetalation to chiral δ-lactones with multiple stereocenters.

Fielded surface detection systems rely on contact with either the liquid contamination itself or the associated chemical vapor above the contaminated surface and do not provide a standoff or remote detection capability. Conversely, standoff chemical vapor sensing techniques have not shown efficacy in detecting those contaminants as liquids or solids on surfaces. There are a number of optical or spectroscopic techniques that could be applied to this problem of standoff chemical detection on surfaces. The three techniques that have received the most interest and development are laser induced breakdown spectroscopy (LIBS), fluorescence, and Raman spectroscopy. Details will be presented on the development of these techniques and their applicability to detecting CBRNE contamination on surfaces.

A new strategy for the synthesis of rare nitrogen-linked eight-membered biaryl ring systems is based on the generation of a highly active intramolecular form of copper.

The method allows the synthesis of various derivatives including ester (XIV) as the immediate precursor of the antiinflammatory drug tolmetin (XV).

Recent advances in the application of kinetic isotope effects to enzyme-catalyzed reactions have provided reliable information for enzymatic transition state structures. A method is presented for quantifying the similarity of substrates and inhibitors with their enzyme-stabilized transition states. On the basis of transition-state stabilization theory for enzymatic reactions, molecules most similar to the transition state structure bind with greatest affinity. Molecular similarity measures are applied to compare substrates, competitive inhibitors, and transition state inhibitors with the transition state structures stabilized by the enzymes AMP deaminase, adenosine deaminase, and AMP nucleosidase. (R)- and (S)-Coformycin 5‘-phosphate are inhibitors for AMP deaminase, with the R-species superior to its enantiomer. Formycin 5‘-phosphate 4-aminopyrazolo[3,4-d]pyrimidine-1-ribonucleotide, and tubercidin 5‘-phosphate inhibit AMP nucleosidase. The transition state for adenosine deaminase is analogous to that fo...

Platinized tin oxide (Pt/SnO x ) and gold supported on manganese oxide (Au/MnO x ) catalysts have been shown to be good CO oxidation catalysts at low temperatures (30–100°C). The performance of these catalysts has been compared by reacting mixtures of CO and OZ and He under similar conditions. The Au/MnO x catalyst is superior to Pt/SnO x catalysts with regard to both activity and decay characteristics under the conditions examined. As expected, Au/MnO x catalysts exhibit greater activity as the reaction gas mixture becomes more oxidizing.

Cross-coupling reactions of various organocopper reagents with α-(mesyloxy)allylsilanes have been evaluated for stereoselective β,β-disubstituted vinylsilane synthesis. S N 2′ displacements with RMgBr/CuCN(cat.) reagents proceeded in high yields (84»94%) and E -selectivities (10:1 » 38:1) in THF at −78°C.

The presence of a removable 1-(trimethylsilyl) residue greatly increases the chelation-controlled diastereoselectivity in alkenylcuprate additions to chiral β-alkoxyaldehydes. Several methods for protiodesilylation of the resultant allylic alcohols [5 » 2b (R=Me3SiCH2CH2OCH2-, PhCH2OCH2-, and PhCH2-)] are compared.

The kinetics of the photochemical (1,7)-sigmatropic shift of 1,3,5-cycloheptatriene (CHT) are determined by two-pulse, one-color, time-resolved UV resonance Raman spectroscopy. An amplified, synchronously pumped dye laser is frequency doubled, providing separate pump and probe pulses at 284 nm with 1.7-ps time resolution. The difference spectra reveal the presence of three scattering components: vibrationally relaxed, vibrationally unrelaxed, and excited-state CHT. Scattering from vibrationally relaxed CHT rises with a time constant of 26 {plus_minus} 10 ps. Scattering from vibrationally unrelaxed CHT appears with a time constant of 26 {plus_minus} 10 ps and decays with a time constant of 15 {plus_minus} 5 ps. Scattering from the excited state of CHT appears and decays within the time resolution of the instrument. The identical appearance kinetics of vibrationally relaxed and unrelaxed CHT demonstrates that population of the ground state followed by rapid intramolecular vibrational relaxation is complete in 26 ps, producing a Boltzmann population which vibrationally cools in 15 ps. These results show that the solution-phase photochemical sigmatropic shift in CHT is complete in 26 ps. 43 refs., 7 figs.

Photoproduct formation, vibrational, and conformational relaxation kinetics in the photochemical ring-openings of 1,3-cyclohexadiene (CHD) and α-phellandrene (α-PHE) are determined by picosecond, time-resolved UV Stokes and anti-Stokes resonance Raman spectroscopy. The frequency-doubled output from an amplified, synchronously pumped dye laser system was used to perform transient, two-color resonance Raman Stokes experiments on the photoconversion of CHD to cis-hexatriene (c-HT) and of α-PHE to 3,7-dimethyl-1,3,5-octatriene (OT). The appearance time of the Stokes scattering from ground-state c-HT is 6±1 ps, while that of OT is 11±2 ps. In both reactions, the photoproduct anti-Stokes ethylenic intensity appears with a time constant of 8±2 ps and decays in 9±2 ps

An enantioselective total synthesis of nagilactone F is described. Functionalized tricyclic intermediate 3 was prepared using a high-yielding acetal-initiated/vinylsilane-terminated polyene cyclization of 5. Intramolecular alkoxy radical-mediated remote functionalization established the D-ring of the nagilactone system.

Cyclization of the radicals derived from Cbond homolysis as well as via 1,5-hydrogen atom transfer afforded tetrahydrofurans in high yield. An alternative anionic cyclization method provided the anti diastereomer preferentially.

A variety of 2-heterocycle substituted 3-phenysulfonyl-5-chloroindoles were investigated as replacements for the 2-carboxamide functionality of the potent HIV-1 reverse transcriptase inhibitor L-737, 126. The 2-carboxamide series of compounds typified by L-737,126 have poor solubility. Replacement of the carboxamide moiety with a variety of heterocycles results in a series of potent enzyme inhibitors with equivalent ex vivo antiviral activity and improved physicochemical properties.

A range of novel cobaltolactone complexes are prepared under photolytic conditions from dicarbonylcyclopentadienylcobalt and vinyl epoxides; their subsequent reactivity under a selected series of reaction conditions is described.

Differential functionalization of the nearly symmetrical bis(dihydropyran) 3 is described, leading to the C(20)→C(36) halichondrin B precursor 1. Double hydroboration, regioselective mono-protection of the resulting diol and two-directional chain extension are featured.

Modular assembly routes to cyclic hydropyran oligolides of diverse structures are described. Macrolactonization of the appropriate tris(hydropyran) hydroxy acid provided compounds 1–8 , whereas macrocycles 9–13 resulted from the cyclodimerization, cyclotrimerization, and cyclotetramerization of the bis- or tris(hydropyran) seco acids, utilizing the “normal” or “modified” Yamaguchi lactonization conditions.

We report a high yielding approach to N-aryl tetrahy- droisoquinolines and tetrahydroquinolines in one step from readily available starting materials. We have used this methodology to pre- pare the full carbon skeleton of the ring system of ancistrocladinium A in one step.